3-53824514-C-T

Variant names:

• chr3-53824514-C-T
• rs7626693
• NM_018397.5:c.-59-447G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018397.5(CHDH):​c.-59-447G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,162 control chromosomes in the GnomAD database, including 15,727 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (15727 hom., cov: 33)
• Consequence: CHDH NM_018397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 10 publications found

Genes affected

CHDH (HGNC:24288): (choline dehydrogenase) The protein encoded by this gene is a choline dehydrogenase that localizes to the mitochondrion. Variations in this gene can affect susceptibility to choline deficiency. A few transcript variants have been found for this gene, but the full-length nature of only one has been characterized to date. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018397.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHDH	NM_018397.5	MANE Select	c.-59-447G>A		intron	N/A	NP_060867.2	Q8NE62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHDH	ENST00000315251.11	TSL:1 MANE Select	c.-59-447G>A		intron	N/A	ENSP00000319851.5	Q8NE62
	CHDH	ENST00000959593.1		c.-506G>A		5_prime_UTR	Exon 1 of 7	ENSP00000629652.1
	CHDH	ENST00000875879.1		c.-59-447G>A		intron	N/A	ENSP00000545938.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63951 AN: 152044 Hom.: 15717 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.457

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63975 AN: 152162 Hom.: 15727 Cov.: 33 AF XY: 0.422 AC XY: 31347 AN XY: 74368

African (AFR) AF: 0.150 AC: 6219 AN: 41540

American (AMR) AF: 0.454 AC: 6937 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1645 AN: 3470

East Asian (EAS) AF: 0.579 AC: 2981 AN: 5150

South Asian (SAS) AF: 0.584 AC: 2819 AN: 4824

European-Finnish (FIN) AF: 0.474 AC: 5011 AN: 10572

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36705 AN: 67994

Other (OTH) AF: 0.459 AC: 971 AN: 2114

Alfa AF: 0.435 Hom.: 3191

Bravo AF: 0.405

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.75
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7626693; hg19: chr3-53858541;